Modeling Drug Responses and Evolutionary Dynamics using Patient-Derived Xenografts Reveals Precision Medicine Strategies for Triple Negative Breast Cancer.

The inter- and intra-tumor heterogeneity of triple negative breast cancers (TNBC), which is reflected in diverse drug responses, interplays with tumor evolution. Here, we developed a preclinical experimental and analytical framework using treatment-naive TNBC patient-derived tumor xenografts (PDTX) to test their predictive value in personalized cancer treatment approaches. Patients and their matched PDTX exhibited concordant drug responses to neoadjuvant therapy using two trial designs and dosing schedules.

Therapeutic Approaches for Non-Melanoma Skin Cancer: Standard of Care and Emerging Modalities.

Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide. Skin exposure is the leading risk factor for initiating NMSC. Ultraviolet (UV) light induces various genomic aberrations in both tumor-promoting and tumor-suppressing genes in epidermal cells.

The effects of simulated monocular and binocular vision impairment on football penalty kick performance.

Sports performance is relatively robust under high levels of binocular blur. However, the limited research studies investigating monocular impairments has shown it has a larger impact on sport performance. This research study is relevant for classification in sports for athletes with vision impairment (VI), where visual acuity (VA) from the better eye is used during classification.

Unraveling the Functional Heterogeneity of Human Skin at Single-Cell Resolution.

The skin consists of several cell populations, including epithelial, immune, and stromal cells. Recently, there has been a significant increase in single-cell RNA-sequencing studies, contributing to the development of a consensus Human Skin Cell Atlas. The aim is to understand skin biology better and identify potential therapeutic targets.

Extracellular vesicles in mycobacteria: new findings in biogenesis, host-pathogen interactions, and diagnostics.

Since the discovery of extracellular vesicles (EVs) in mycobacterial species 15 years back, we have learned that this phenomenon is conserved in the genus and has critical roles in bacterial physiology and host-pathogen interactions. (), the tuberculosis (TB) causative agent, produces EVs both and including a diverse set of biomolecules with demonstrated immunomodulatory effects. Moreover, EVs (MEVs) have been shown to possess vaccine properties and carry biomarkers with diagnostic capacity.

Therapy Intensity Level Scale for Traumatic Brain Injury: Clinimetric Assessment on Neuro-Monitored Patients Across 52 European Intensive Care Units.

Intracranial pressure (ICP) data from traumatic brain injury (TBI) patients in the intensive care unit (ICU) cannot be interpreted appropriately without accounting for the effect of administered therapy intensity level (TIL) on ICP. A 15-point scale was originally proposed in 1987 to quantify the hourly intensity of ICP-targeted treatment. This scale was subsequently modified-through expert consensus-during the development of TBI Common Data Elements to address statistical limitations and improve usability.

Hyperpolarised C-MRI using C-pyruvate in breast cancer: A review.

Tumour metabolism can be imaged with a novel imaging technique termed hyperpolarised carbon-13 (C)-MRI using probes, i.e., endogenously found molecules that are labeled with C.

A digital mask to safeguard patient privacy.

The storage of facial images in medical records poses privacy risks due to the sensitive nature of the personal biometric information that can be extracted from such images. To minimize these risks, we developed a new technology, called the digital mask (DM), which is based on three-dimensional reconstruction and deep-learning algorithms to irreversibly erase identifiable features, while retaining disease-relevant features needed for diagnosis. In a prospective clinical study to evaluate the technology for diagnosis of ocular conditions, we found very high diagnostic consistency between the use of original and reconstructed facial videos (κ ≥ 0.

Huntingtin turnover: modulation of huntingtin degradation by cAMP-dependent protein kinase A (PKA) phosphorylation of C-HEAT domain Ser2550.

Huntington's disease (HD) is a neurodegenerative disorder caused by an inherited unstable HTT CAG repeat that expands further, thereby eliciting a disease process that may be initiated by polyglutamine-expanded huntingtin or a short polyglutamine-product. Phosphorylation of selected candidate residues is reported to mediate polyglutamine-fragment degradation and toxicity. Here to support the discovery of phosphosites involved in the life-cycle of (full-length) huntingtin, we employed mass spectrometry-based phosphoproteomics to systematically identify sites in purified huntingtin and in the endogenous protein by proteomic and phosphoproteomic analyses of members of an HD neuronal progenitor cell panel.

Decomposing biophotovoltaic current density profiles using the Hilbert-Huang transform reveals influences of circadian clock on cyanobacteria exoelectrogenesis.

Electrons from cyanobacteria photosynthetic and respiratory systems are implicated in current generated in biophotovoltaic (BPV) devices. However, the pathway that electrons follow to electrodes remains largely unknown, limiting progress of applied research. Here we use Hilbert-Huang Transforms to decompose Synechococcus elongatus sp.

BRD2 interconnects with BRD3 to facilitate Pol II transcription initiation and elongation to prime promoters for cell differentiation.

The bromodomain and extraterminal motif (BET) proteins are critical drug targets for diseases. The precise functions and relationship of BRD2 with other BET proteins remain elusive mechanistically. Here, we used acute protein degradation and quantitative genomic and proteomic approaches to investigate the primary functions of BRD2 in transcription.

A Phase I Study Investigating AZD8186, a Potent and Selective Inhibitor of PI3Kβ/δ, in Patients with Advanced Solid Tumors.

Purpose: To characterize safety and tolerability of the selective PI3Kβ inhibitor AZD8186, identify a recommended phase II dose (RP2D), and assess preliminary efficacy in combination with abiraterone acetate or vistusertib.

Patients And Methods: This phase I open-label study included patients with advanced solid tumors, particularly prostate cancer, triple-negative breast cancer, and squamous non-small cell lung cancer. The study comprised four arms: (i) AZD8186 monotherapy dose finding; (ii) monotherapy dose expansion; (iii) AZD8186/abiraterone acetate (with prednisone); and (iv) AZD8186/vistusertib.

The Antarctic Weddell seal genome reveals evidence of selection on cardiovascular phenotype and lipid handling.

The Weddell seal (Leptonychotes weddellii) thrives in its extreme Antarctic environment. We generated the Weddell seal genome assembly and a high-quality annotation to investigate genome-wide evolutionary pressures that underlie its phenotype and to study genes implicated in hypoxia tolerance and a lipid-based metabolism. Genome-wide analyses included gene family expansion/contraction, positive selection, and diverged sequence (acceleration) compared to other placental mammals, identifying selection in coding and non-coding sequence in five pathways that may shape cardiovascular phenotype.

Improving Few- and Zero-Shot Reaction Template Prediction Using Modern Hopfield Networks.

Finding synthesis routes for molecules of interest is essential in the discovery of new drugs and materials. To find such routes, computer-assisted synthesis planning (CASP) methods are employed, which rely on a single-step model of chemical reactivity. In this study, we introduce a template-based single-step retrosynthesis model based on Modern Hopfield Networks, which learn an encoding of both molecules and reaction templates in order to predict the relevance of templates for a given molecule.

Body mass index categories and anxiety symptoms among adults aged ≥ 50 years from low and middle income countries.

Background: Body weight may be a risk factor for anxiety; however, there is a scarcity of studies on this association in older adults especially from low and middle income countries (LMICs). Therefore, we investigated the association between body mass index (BMI) and anxiety symptoms among adults aged ≥ 50 years from 6 LMICs.

Methods: Cross-sectional, community-based, nationally representative data from the World Health Organization (WHO) Study on global AGEing and adult health (SAGE) were analyzed.

Efficacy of pharmacologic treatment in tinnitus patients without specific or treatable origin: A network meta-analysis of randomised controlled trials.

Background: Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear.

Financial and Mental Health Concerns of Impoverished Urban-Dwelling Bangladeshi People During COVID-19.

The COVID-19 pandemic has impacted the physical, mental and financial health of many individuals. Individuals living in impoverished crowded settings may be particularly vulnerable to COVID-19-related stressors. How substantially marginalized groups like impoverished urban-dwelling individuals have been impacted during this pandemic is poorly understood.

MRI of the endometrium - from normal appearances to rare pathology.

MRI was recently included as a standard pre-operative diagnostic tool for patients with endometrial cancer. MR findings allow a better risk assessment and ultimately guides the surgical planning. Therefore, it is vital that the radiological interpretation is as accurate as possible.

Predicting future from past: The genomic basis of recurrent and rapid stickleback evolution.

Similar forms often evolve repeatedly in nature, raising long-standing questions about the underlying mechanisms. Here, we use repeated evolution in stickleback to identify a large set of genomic loci that change recurrently during colonization of freshwater habitats by marine fish. The same loci used repeatedly in extant populations also show rapid allele frequency changes when new freshwater populations are experimentally established from marine ancestors.